title: Enhanced absorption and tissue distribution of paclitaxel following oral administration of DHP 107, a novel mucoadhesive lipid dosage form.
abstract: OBJECTIVE
  This study was conducted to examine the absorption and tissue distribution characteristics of paclitaxel-loaded DHP 107, a Cremophor EL-free, mucoadhesive lipid oral dosage form.
  
  
  METHODS
  DHP 107 was orally administered to mice at 10, 20 and 40 mg/kg doses. For comparison purposes, Taxol was i.v. injected at 5, 10 and 20 mg/kg doses. Drug levels were determined in plasma and tissues by validated HPLC assays. The absolute bioavailability and the relative distribution to various tissues were calculated as a function of dose.
  
  
  RESULTS
  The dose-normalized plasma AUC(DHP 107)/AUC(Taxol) ratios calculated at comparable AUC values ranged from 14.6 to 29.0%. In contrast, relative tissue distribution ratios calculated as the dose-normalized AUC(DHP 107)/AUC(Taxol) were as high as 342.0, 139.0, 112.9 and 108.2% for stomach, small intestine, large intestine and ovary, respectively.
  
  
  CONCLUSIONS
  Oral administration of DHP 107 provided a substantial systemic absorption of paclitaxel. Furthermore, the relative distribution ratios of DHP 107 at doses of 20 and 40 mg/kg were higher for stomach, small intestine, large intestine, and ovary than the systemic bioavailability, providing a basis for therapeutic advantages.
authors.affiliation: College of Pharmacy, Catholic University of Daegu, Gyeongsan-si, Gyeongbuk, South Korea.
authors.forename: Beom Soo
authors.initials: BS
authors.lastname: Shin
authors.forename: Hyoung Jun
authors.initials: HJ
authors.lastname: Kim
authors.forename: Seok Hyun
authors.initials: SH
authors.lastname: Hong
authors.forename: Jong Bong
authors.initials: JB
authors.lastname: Lee
authors.forename: Sang Wook
authors.initials: SW
authors.lastname: Hwang
authors.forename: Mann Hyung
authors.initials: MH
authors.lastname: Lee
authors.forename: Sun Dong
authors.initials: SD
authors.lastname: Yoo
mesh_terms: D000268:Adhesiveness; D000284:Administration, Oral; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D005079:Excipients / Q000737:chemistry*; D005260:Female; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D008055:Lipids / Q000737:chemistry*; D051379:Mice; D008813:Mice, Inbred ICR; D017239:Paclitaxel / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D005079:Excipients; D008055:Lipids; D017239:Paclitaxel